PROJECT SUMMARY Cataract surgery is the most common medical procedure in the aged population, with nearly 3 million patients treated annually in the U.S. alone. During this procedure, the cataractous lens fibers are removed through a permanent hole called a continuous circular capsulorhexis (CCC) placed in the anterior portion of the lens capsule and replaced with an artificial intraocular lens (IOL). In response, lens epithelial cells of the remnant lens capsule become fibrotic, causing distortion and opacification of the lens capsule that can lead to visual disturbances to the patient. This fibrotic response is particularly aggressive in accommodative IOLs (AIOLs), which attempt to restore the ability of the lens to change focus from distant to near objects. Although numerous AIOL designs have been proposed, their efficacy is limited as the fibrotic response renders them incapacitated. Our previous work has strongly suggested that the permanent disruption to the stress field of the lens capsule during cataract surgery drives the fibrotic response and remodeling. This remodeling process ultimately changes IOL efficacy both in terms of the fibrotic response and, when applicable, accommodative function. Despite these associations, few models have been developed to assess lens capsule-IOL interactions, and no model has considered altered mechanics after cataract surgery. Therefore, the goal of this project is to develop the first 3- D finite element model of the post-surgical lens capsule to consider altered stress-mediated adaptations over time after cataract surgery. The model will be used to accomplished two aims. First, we will test whether it can predict mechanical and biological remodeling of the lens capsule with implanted tension ring (used to quantify the degree of fibrotic contraction of the lens capsule after cataract surgery). Second, the model will be used to predict the efficacy of an AIOL over time after implantation, as a function of CCC size. Both aims will be compared to reported empirical data to validate the predictive capability of the model. This work is expected to provide quantitative characterization of the mechanical disturbance to the lens capsule over time after cataract surgery and insights into how it drives the cell-mediated remodeling process. This is important for predicting the efficacy of an implanted IOL and developing a functional AIOL, which is widely considered to be the last unconquered frontier in refractive eye surgery. In addition, the results of this model will provide insights into mechanical drivers of fibrotic cellular behaviors that will improve our understanding of capsular fibrosis and mechanisms of implanted intraocular lens dysfunction. These insights will inform and direct our experimental efforts to further understand mechanical and biological drivers of capsular fibrosis. This understanding can also be translated to shed light on the process of fibrosis, in general, which is thought to be associated with nearly half of all deaths worldwide, to better understand the etiology of diseases in other parts of the body.